Drugs indication Flashcards
Midazolam
SA
- Anxiety
- Induction of general anesthesia
- procedural sedation
Triazolam
SA
- insomnia
- hypnotics
Alprazolam
IA
- Anxiety
- Panic disorder
- Sedative
Clonazepam
IA
- Panic disorder
- seizure
- Anti-convulsant
Lorazepam
IA
- Anxiety
- insomnia
- status epilepticus
- sedative
oxazepam
IA
- Alcohol withdrawal syndrome
- anxiety
Temazepam
IA
- Insomnia
- Hypnotics
Chlordiazepoxide
LA
- Alcohol withdrawal syndrome
- anxiety
Flurazepam
LA
- insomnia
Diazepam
LA
- Alcohol withdrawal syndrome
- anxiety
- sedation
- status epilepticus
- seizure
- hypnotics
- pre-anaesthetics
- anti-convulsant
- refractory seizure
- adjunct skeletal muscle spasm
Anxiety
Midazolam (SA)
Alprazolam (IA)
Lorazepam (IA)
Diazepam (LA)
Panic disorder
Alprazolam (IA)
Clonazepam (IA)
insomnia
Triazolam (SA)
lorazepam (IA)
temazepam (IA)
Flurazepam (LA)
Alcohol withdrawal syndrome
Oxazepam (IA)
Chlordiazepoxide (LA)
Diazepam (LA)
Status epilepticus
Lorazapam (IA)
Diasepam (LA)
Chlorpromazine
Typical Antipsychotics
(antiD2)
M1: Dry mouth, constipation, blurred vision
H1: sedation, weight gain
A1: Postural hypotension,dizziness.
D2: EPS (Acute Dystonias, Tardive Dyskinesia, Akath
Haloperidol
Typical Antipsychotics
(antiD2)
A1: Postural hypotension,dizziness.
D2: EPS (Acute Dystonias, Tardive Dyskinesia, Akathisia)
Clozapine
Atypical antipsychotics
M1: Dry mouth, constipation, blurred vision
H1: sedation, weight gain
A1: Postural hypotension,dizziness.
- agranulocytosis (Agranulocytosis is the lack of granulocyte type white blood cells)
(● Regular blood counts are required to monitor patients.)
- Diabetes
- wt gain
Led to development of compounds related to clozapine but without this adverse effect e.g. olanzapine.
olanzapine
Atypical antipsychotics
M1: Dry mouth, constipation, blurred vision H1: sedation, weight gain A1: Postural hypotension,dizziness. - Diabetes - wt gain
risperidone
Atypical antipsychotics
Postural hypotension, reflex tachycardia
● Due to α1-adrenoceptor antagonism.
- Diabetes
- wt gain
Amisulpride
Amisulpride is a selective D2/D3 antagonist (but recently also reported to have 5-HT7 antagonism). For an atypical antipsychotic, it has an atypical pattern of receptor affinities.
Few side-effects due to selectivity for D2 / D3 receptors.
Absence of α-adrenoceptor block, antihistaminergic, and anticholinergic side-effects.
Adverse effects on mammary glands and tissues:
● Increased prolactin secretion due to block of dopamine receptors in the anterior pituitary gland.
● Breast swelling, pain, and lactation.
● Presents as gynaecomastia in males.
Aripiprazole
partial agonists
H1: sedation, weight gain
A1: Postural hypotension,dizziness.
Typical antipsychotics
chlropromazine
Fluphenazine
Haloperidol
Trifluoperazine
Atypical antipsychotics
Clozapine olanzapine risperidone Amisulpride Aripiprazole
Benzodiazepine antagonist
Flumazenil
LA Barbiturates and their indication
Anticonvulsant
- Phenobarbital
1-2days
SA Barbiturates and their indication
Sedative and hypnotic
- pentobarbital
- amobarbital
3-8hr
US Barbiturates and their indication
IV induction of anesthesia
- Thiopental
20min
BZD ADR
– Drowsiness, confusion, amnesia.
– Impaired muscle co-ordination (impairs manual skills).
– Can cause severe respiratory depression, especially used concurrently with alcohol.
Treatment is by flumazenil, a benzodiazepine antagonist.
Barbiturates ADR
– Can cause severe respiratory depression, especially used concurrently with alcohol.
Levodopa
1st line parkinson
- First available in 1960s
- Dopamine precursor, “2-in-1” preparation with carbidopa, a DOPA-decarboxylase inhibitor to prevent side effects due to excess DA in PNS (Eg, Levodopa + carbidopa: Sinemet)
-L-dopa –> dopamine ( enzyme = DOPA decarboxylase)
therefore prevent conversation of dopa to dopamine at PNS.
Carbidopa cannot pass BBB. so only stay at PNS. and also increase half life of dopa
Strategy to increase dopamine synthesis
Side effect of levodopa
– Short term: nausea, vomiting, postural hypotension
– Long term: motor fluctuations and dyskinesia (10%/yr)
– Although levodopa is the most efficacious drug for the symptomatic management of both early and late Parkinson’s disease, the dose of levodopa should be kept to the minimum necessary to achieve good motor function.
Entacapone(Comtan®) or Tolcapone (Tasmar®)
Strategy: inhibit dopamine breakdown with COMT inhibitors
- blocks COMT conversion of dopamine into an inactive form
- more levodopa is available to enter the brain (reduces required dose)
- only effective if used with levodopa
- increases duration of each dose of levodopa, beneficial in treating “wearing off” responses
Entacapone(Comtan®) or Tolcapone (Tasmar®)
Entacapone(Comtan®) or Tolcapone (Tasmar®)
- Increase abnormal movements (dyskinesias)
- Liver dysfunction (Tolcapone)
- Nausea, diarrhea
- Urinary discoloration
- Visual hallucinations
- Daytime drowsiness, sleep disturbances
Selegiline or rasagiline(Azilect®)
Strategy: inhibit dopamine breakdown with MAO-B inhibitors
- Mild antiparkinson activity
- Inhibits enzyme monoamine oxidase B, interferes with breakdown of dopamine
- Laboratory studies suggest that it may delay the nigral brain cell degeneration
Selegiline is efficacious as a symptomatic monotherapy and may be used in early stages of Parkinson’s disease.
Selegiline or rasagiline(Azilect®) ADR
- Heartburn, loss of appetite
- Anxiety, palpitation, insomnia
- Nightmares, visual hallucination
Bromocriptine
Dopamine agonists • Used since 1970s, adjunct or monotherapy • Available as – Bromocriptine(Parlodel®) – Pergolide(Celance®, Permax®) – Ropinirole(Requip®)
- Act directly on dopamine receptors in the brain to reduce the symptoms of PD
- Antiparkinsonianeffects not superior to levodopa (levodopa still the gold standard)
- Prevent or delay onset of motor complications
In younger Parkinson’s disease patients, therapy should commence first with dopamine agonists rather than levodopa.
Pergolide
Dopamine agonists • Used since 1970s, adjunct or monotherapy • Available as – Bromocriptine(Parlodel®) – Pergolide(Celance®, Permax®) – Ropinirole(Requip®)
- Act directly on dopamine receptors in the brain to reduce the symptoms of PD
- Antiparkinsonianeffects not superior to levodopa (levodopa still the gold standard)
- Prevent or delay onset of motor complications
In younger Parkinson’s disease patients, therapy should commence first with dopamine agonists rather than levodopa.
Ropinirole
Dopamine agonists • Used since 1970s, adjunct or monotherapy • Available as – Bromocriptine(Parlodel®) – Pergolide(Celance®, Permax®) – Ropinirole(Requip®)
- Act directly on dopamine receptors in the brain to reduce the symptoms of PD
- Antiparkinsonianeffects not superior to levodopa (levodopa still the gold standard)
- Prevent or delay onset of motor complications
In younger Parkinson’s disease patients, therapy should commence first with dopamine agonists rather than levodopa.
dopamine agonists side effect
– Bromocriptine(Parlodel®)
– Pergolide(Celance®, Permax®)
– Ropinirole(Requip®)
- ‘Ergot’ derivative –fibrosis
- Pedal edema
- Somnolence (ropinirole)
- Restrictive valvular heart disease (pergolide)
Dopaminergic drug
Levodopa (+/-carbidopa)
Entacapone/ Tolcapone
Selegiline/ rasagiline
Bromocriptine/ pergolide/ ropinirole
non dopaminergic drug
amantadine
trihexyphenidyl
Amantadine
• Antiviral agent, accidentally discovered to have mild antiparkinsonianeffect (tremor, rigidity, bradykinesia, dyskinesia).
• Given as monotherapy or adjunct to levodopa.
• Mechanism of action:
– Enhance release of stored dopamine
– Inhibit presynaptic uptake of catecholamine
– Dopamine receptor agonist
– NMDA receptor antagonist (anti-glutamate)
• Antidyskinetic
Amantadine may be considered as therapy to reduce dyskinesia in patients with Parkinson’s disease who have motor fluctuations
Amantadine ADR
Side effects limit its use in advanced disease:
–Cognitive impairment (inability to concentrate), hallucination, insomnia, nightmares, livedo reticularis (Venule swelling due to thromboses –> mottled reticulated discoloration of limbs).
Trihexyphenidyl(Artane®)
anticholinergics
Advantages:
– May be effective in controlling tremor
– Peripherally acting agents may be useful in treating sialorrhoea
Anticholinergic agents may be used as symptomatic monotherapy or as an adjunct to levodopa to treat tremors and stiffness in Parkinson’s disease.
Trihexyphenidyl(Artane®) ADR
• Side effects (especially in elderly): – Dry mouth, sedation, constipation, urinary retention, delirium, confusion, hallucinations
Medication for epilepsy
Antiepileptics (I)
Phenytoin
carbamazepine
Valproate
Antiepileptics (II) Pregabalin Vigabatrin Lamotrigine Others eg, BZDs
BZD is additive therefore not a good choice coz epilepsy is lifelong
Phenytoin
Blockade of voltage-depedent Na+ channels.
• Suitable for all types of seizures except absence seizures.
• A relative narrow therapeutic range (plasma concentration 40-100 μM), saturation kinetics and consequent non-linear relationship between dose and plasma concentration necessitates titration and monitoring.
ADR of Phenytoin
- hypothyroidism
- gum hypertrophy
- confusion and difficulty balancing –> involve cerebellar and vestibular system -> ataxia, vertigo
- craniofacial abnormalities with prenatal exposure
- folate and B12 deficiency
- immunosuppresant
- hirsutism
overdose = convusion cerebellar vestibular B12 / folate deficiency
hypersensitivity
- morbiliform
lupus like
megaloblastic anaemia
teratogenic
Carbamazepine
Blockade of voltage-depedent Na+ channels (like phenytoin).
• Suitable for all types of seizures except absence seizures.
• Hepatic enzyme (CYP450) inducer, T½ shortens with repeated doses —–> accelerates elimination of other drugs.
Carbamazepine ADR
Dose dependent
- GI Upset
- Diplopia
- nystamus
- drowsiness
- folate vit D def
- antidiuretic effect
Overdose
- Ataxia
- Confusion
- Behavioral-disturbance
hypersensitivity
- Bone marrow
- Rashes
- SLE
- SJS
- Lymphadenopathy
- Hepatitis
Teratogenic
- In animals
- In human??
Valproate
- Blockade of voltage-dependent Na+ and Ca2+ channels.
- Also inhibits GABA transaminase —-> increased GABA
- Suitable for all types of seizures, including absence seizures.
- Strongly bound to plasma proteins, displaces other antiepileptics.
Valproate ADR
Dose dependent
- GI upset
- Sedation
- wt gain
- hair loss
Hypersensitivity
- hepatotoxicity
- Thrombocytopenia
Teratogenic
- Spina bifida
- CVS
- Orofacial
- Digital
pregabalin
second gen AED
potentiate the release of GABA
–GABA analogue, increases synaptic GABA –> GABA receptor mediated Cl- currents resulting in hyperpolarization.
–Also acts on voltage-gated Ca2+channels.
–Besides GAD (ANXIETY), also used as add-on therapy for partial seizures (SEIZURE)
pregabain ADR
–Adverse effects, mainly SEDATION, may be associated with emergence of worsening of SUICIDAL thoughts.
therefore not good for depression
Buspirone
–A serotonin 5-HT1A receptor partial agonist. Also binds dopamine receptors.
–Indicated for GAD but anxiolytic effects takes 1-2 weeks.
–Lacks anticonvulsant and muscle relaxant properties.
Propanolol
A beta-adrenergic receptor antagonist (“betablocker”).
–Used for treating performance anxiety and social phobias.
–Reduces physical symptoms associated with adrenergic activation.
–Contraindicated in patients with asthma and heart conditions.
Hydroxyzine
–A first generation antihistamine with activities on serotonergic and α-adrenergic receptors.
–Anxiolytic effects attributed to antagonism of serotonin 5-HT2 receptors.
–Has low addictive potential compared to BZDs and barbiturates.
–Because of antihistamine activities, also helps with itching.
vigabatrin
second gen AED
–Inhibits GABA transaminase —> increased synaptic GABA (» valproate).
–Useful in all types of seizures, including those refractory to other AEDs.
vigabatrin ADR
–Side effects: Sedation, behavioural and mood changes (occasionally psychosis), visual field defects.
Lamotrigine
second gen AED
- –Blockade of voltage-depedent Na+ channels.
–Also inhibits glutamate release.
–For all types of seizures.
Lamotrigine
–Side effects: Dizziness, sedation, rashes.
BZD and barbiturates
epilepsy also
Phenelzine
An irreversible MAO inhibitor.
depression
MAO inhibitor. ADR
Postural hyoptension
• Probably due to sympathetic block produced by accumulation of dopamine in the cervical (neck) ganglia, where is acts as an inhibitory transmitter
Restlessness and insomnia due to central nervous system (CNS) stimulation
MAOI DDI FDI
1) pethidine
2) cheese
3) concentrated yeast product (eg marmite)
4) tyramine (amines in food)
Should not be combined with or other drugs enhancing serotoninergic function (e.g. pethidine)
cause–> • Hyperexcitability, increased muscular tone, myoclonus (jerking, involuntary movements), loss of consciousness
The cheese reaction
- Major limitation on the use of MAOIs.
- Acute hypertension, giving severe throbbing headache, and occasionally intracranial haemorrhage.
Less likely to occur with MAO-A selective, reversible MAOIs (e.g. moclobemide).
Amines (e.g. tyramine) in foods (e.g. cheese) are usually broken down by MAO in the intestines and liver. MAOIs can lead to accumulation of tyramine and a sympathomimetic effect.
Dangerous food interactions with MAO blockers (e.g. acute hypertension).
Tyramine is taken up into adrenergic terminals and competes with NA for the vesicular compartment.
Imipramine, Amitriptyline, nortriptyline
Non-selective for SERT/NET:
Depression
Desipramine
Selective for NET:
Desipramine
TCA ADR
Sedation
•Due to H1 histamine receptor antagonism
•Tolerance to sedation can develop in 1-2 weeks
Postural hypotension
•Due to α-adrenoceptor sympathetic block
Dry mouth, blurred vision, constipation
•Due to muscarinic receptor antagonism
Risk of drug induced cardiac dysrhythmias
•Perhaps due to block of HERG potassium channel
SSRI adv
Low affinity for α adrenoceptors ——–>
Lack of cardiovascular effects, safer in overdose
Lack of effect at histamine receptors ————–>
Reduced sedation
Low affinity for muscarinic cholinergic receptors ——–>
Minimal anticholinergic side effects (e.g. dry mouth and constipation)
Overall SSRIs are safer in overdose and less side effects lead to better compliance.
Adverse effects of TCAs lead to prescription of subtherapeutic doses.
Improved adverse effect profile of SSRIs leads to better compliance and so prescription of more adequate doses.
basically good
1) efficacy
2) safety
3) tolerability
1st line therapy. but not perfect…..
• Only 2/3 get remission
• Adverse effects especially at start
• Discontinuation can be a problem in some
Fluoxetine
Citalopram
ADR
Nausea
Insomnia
Sexual dysfunction
N AND I
- May be discontinuation/rebound symptoms of withdrawal when plasma levels of drug
SSRI-induced sexual dysfunction
Men = delayed ejaculation
Women = delayed or blocked orgasm (anorgasmia)
Reported by up to 50% of patients on SSRIs
But rarely [<10%] leads to discontinuation
Due to increased stimulation of 5HT2 receptors
Cyproheptadine or other 5HT2 blockers
can be given to prevent SSRI-induced sexual dysfunction
Citalopram still has some histamine receptor antagonism leading to sedation.
Reboxetine
Noradrenaline Reuptake Inhibitors (NARIs)
Depression
Fluoxetine
Citalopram
SSRI
depression
Serotonin syndrome
1) serotonin syndrome Severe reaction can result from drug-drug interactions with other drugs increasing serotoninergic activity (e.g. MAOIs). Effects include: tremor hyperthermia cardiovascular collapse
Reboxetine
Noradrenaline Reuptake Inhibitors (NARIs)
New drug so adverse effects not well described.
Dry mouth (11 %)
Constipation (9 %)
Insomnia (approx. 9 %)
- Probably due to increased noradrenergic activity in the central nervous system.
Tachycardia (approx. 3%)
- Probably due to increased availability of NA at sympathetic “fright, flight or fight” synapses.
Venlafaxine
desvenlafaxine
duloxetine
Serotonin and Noradrenaline reuptake Inhibitors (SNRIs)
Depression
Serotonin and Noradrenaline reuptake Inhibitors (SNRIs)
adv
Different structure to TCAs and fewer adverse effects than TCAs.
Claimed to work slightly faster than other antidepressants.
Claimed to work better in treatment-resistant patients
Venlafaxine
desvenlafaxine
duloxetine
ADR
Serotoninergic adverse effects similar to SSRIs:
Nausea
Insomnia
Sexual dysfunction
“Serotonin syndrome” when combined with other serotoninergic drugs and MAOIs.
Withdrawal effects may be more common and stronger than for SSRIs and TCAs.
Mirtazapine:
a norepinephrine and specific serotonin antidepressant (NaSSA). Antagonist of adrenergic α2 autoreceptors and 5-HT2C receptor, among others.
Depression
Bupropion:
a norepinephrine-dopamine reuptake inhibitor (NDRI).
Depression
Agomelatine:
agonist of melatonin MT1 and MT2 receptors, less TCA / SSRI-associated side-effects, also helps in sleep disorders.
depression
Ketamine:
a glutamate NMDA receptor antagonist used as an anesthetic, currently evaluated for rapid-onset antidepressant effect.
depression
effect of opioid
Spinal Analgesia
Peripheral Analgesia
Pupil constriction
Supraspinal Analgesia
Cough suppression
Reduced gut motility
Constipation
Dysphoria Respiratory depression Euphoria Severe sedation Sedation
opioid Analgesia:
Analgesia: Codeine, morphine, pethidine
Anaesthetic adjuvant opioid
Anaesthetic adjuvant: Fentanyl
opioid Anti-diarrhoeal:
Anti-diarrhoeal: Diphenoxylate
Cough suppressant / antitussive:
Cough suppressant / antitussive: Codeine
Strong Opioid Agonists
and receptor binding efficacy addiction
Morphine:
Strong m agonist (weaker d and kagonist).
High maximum analgesic efficacy.
High liability for addiction/abuse.
Methadone and Fentanyl:
Strong m agonists (no significant d and kaffinity).
High maximum analgesic efficacy.
High liability for addiction/abuse
Methadone is long-acting (plasma half-life > 24 hrs).
Fentanyl is short-acting (anaesthetic adjuvant).
Pethidine (Meperidine):
Strong m agonist (probably weaker d and kagonist).
Shorter duration of action than morphine (especially in neonate therefore used in labour).
N-demethylated in the liver to norpethidine (hallucinogenic and convulsant effects at high dose)
Restlessness rather than sedation
Antimuscarinic (i.e. parasympatholytic) therefore dry mouth, blurring of vision but no miosis and less spasm of smooth muscle.
Moderate opioid agonists
Codeine / Dihydrocodeine:
Weak m and d agonist (probably not a k agonist).
Low maximum analgesic efficacy.
Moderate liability for addiction/abuse.
~10 % converted to morphine / dihydromorphine.
~10 % of population show reduced analgesic effect due to lack of demethylating enzyme.
Tramadol:
Weak m agonist.
Weak inhibitor of 5-HT and noradrenaline re-uptake
Ondansetron blocks analgesic effect: Also a 5-HT3 agonist?
opioid common adr
Nausea / vomiting
most probably due to actions on the chemoreceptor trigger zone in the area postrema of the medulla (usually reduces with repeated or chronic use).
Constipation
due to reduced gastrointestinal motility (esp. with chronic use).
Miosis (pinpoint pupils)
due to actions in the oculomotor nucleus.
Pinpoint pupil is a diagnostic feature of opioid overdose
But note that mydriasis can also follow if hypoxia occurs.
Urinary retention
due to increased bladder sphincter tone (esp. in patients with prostatic hypertrophy.)
Postural hypotension and bradycardia
due to actions in cardioregulatory nuclei in the medulla.
Drowsiness
Morphine can also trigger histamine release from mast cells
urticaria and itching
bronchoconstriction
hypotension due to vasodilatation
Morphine should be used with caution in asthmatics.
Immunosuppressant effect with long-term use, most likely through CNS effects on the immune system.
opioid withdrawal syndrome
anxiety, irritability, chills, hot flushes, joint pain, lacrimation (tears), rhinorrhea (runny nose), nausea, vomiting, abdominal cramps, diarrohea.
Opioid Antagonists
Naloxone / Naltrexone / Nalmefene:
Strong m antagonism; also d and k antagonism.
Naloxone is short-acting (usually intravenous)
Naltrexone is long-acting (oral administration)
Nalmefene is long-acting (intravenous)
Used to counteract opioid overdose.
Use with extreme caution in patients with opiate dependency as they can precipitate potentially fatal withdrawal syndrome.
Naloxone
Naloxone is short-acting (usually intravenous)
opioid antagonist
Naltrexone
Naltrexone is long-acting (oral administration)
Nalmefene is long-acting (intravenous)
opioid antagonist
Nalmefene
Nalmefene is long-acting (intravenous)
opioid antagonist
